Details

Autor(en) / Beteiligte

• Bolin, Karin
• Imgenberg-Kreuz, Juliana
• Leonard, Dag
• Sandling, Johanna K
• Alexsson, Andrei
• Pucholt, Pascal
• Haarhaus, Malena Loberg
• Almlöf, Jonas Carlsson
• Nititham, Joanne
• Jönsen, Andreas
• Sjöwall, Christopher
• Bengtsson, Anders A
• Rantapää-Dahlqvist, Solbritt
• Svenungsson, Elisabet
• Gunnarsson, Iva
• Syvänen, Ann-Christine
• Lerang, Karoline
• Troldborg, Anne
• Voss, Anne
• Molberg, Øyvind
• Jacobsen, Søren
• Criswell, Lindsey
• Rönnblom, Lars
• Nordmark, Gunnel

Titel

Variants in BANK1 are associated with lupus nephritis of European ancestry

Ist Teil von

• Genes and immunity, 2021-07, Vol.22 (3), p.194-202

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• The genetic background of lupus nephritis (LN) has not been completely elucidated. We performed a case-only study of 2886 SLE patients, including 947 (33%) with LN. Renal biopsies were available from 396 patients. The discovery cohort (Sweden, n = 1091) and replication cohort 1 (US, n = 962) were genotyped on the Immunochip and replication cohort 2 (Denmark/Norway, n = 833) on a custom array. Patients with LN, proliferative nephritis, or LN with end-stage renal disease were compared with SLE without nephritis. Six loci were associated with LN (p < 1 × 10 , NFKBIA, CACNA1S, ITGA1, BANK1, OR2Y, and ACER3) in the discovery cohort. Variants in BANK1 showed the strongest association with LN in replication cohort 1 (p = 9.5 × 10 ) and proliferative nephritis in a meta-analysis of discovery and replication cohort 1. There was a weak association between BANK1 and LN in replication cohort 2 (p = 0.052), and in the meta-analysis of all three cohorts the association was strengthened (p = 2.2 × 10 ). DNA methylation data in 180 LN patients demonstrated methylation quantitative trait loci (meQTL) effects between a CpG site and BANK1 variants. To conclude, we describe genetic variations in BANK1 associated with LN and evidence for genetic regulation of DNA methylation within the BANK1 locus. This indicates a role for BANK1 in LN pathogenesis.